Scientists report unraveling mystery of kids who get old by 10
and World Science staff
Scientists say they are unraveling a longstanding mystery of how a rare disease causes its victims to die in their early teens—apparently of old age.
The answer could do more than help those children, researchers say. It could but also lead to a better understanding of how normal aging happens, and what if anything one could do to stop it.
An estimated one in 8 million children are born with the condition, called Hutchinson-Gilford Progeria Syndrome. They start life in apparent good health but by six to eighteen months develop signs of premature aging, including hair loss, stiff joints, osteoporosis and atherosclerosis. Typically, they die by 13, finished by heart attacks or strokes.
Progeria researchers reported a breakthrough in 2003. They traced the condition to a spontaneous mutation in a gene encoding an important structural component of the cell nucleus, the compartment of a cell that stores our genes.
The nucleus must keep this vital information safe but accessible inside a strong protective envelope. Tough but adaptable molecules called lamins line the inner membrane of this envelope. The progeria mutation causes a defect in one type of lamin, called nuclear lamin A, causing cells to age rapidly.
This left researchers asking: what is it about this defect that causes cells to age so rapidly? And might it have some relevance to normal aging? In other words, is progeria a warp-speed version of normal aging?
In research presented Tuesday at the Annual Meeting of the American Society for Cell Biology in San Francisco, Robert Goldman and his collaborators at Northwestern University and elsewhere say they’ve answered some questions about the defective molecules.
Lamins link together into fibrous structures that hold up the “walls” of the nucleus. They also serve as an internal scaffold for the complex machinery by which our genes copy themselves and direct the working of our bodies, a process called gene expression.
Reporting on two sets of experiments, Goldman et al say that the mutant molecule seems to disrupt key controls of both these processes.
One study found that some of the mutant lamins turn up in the wrong place—too tightly linked to the membranes of the nuclear envelope to be of much help during key stages of cell replication.
The researchers said this would disrupt DNA replication, a probable factor in the rapid march of cells toward premature "senescence," or aging. Whether similar missteps and miscues by nuclear lamins are part of “normal” human aging is the question that draws researchers onward, said Goldman.
Scientists have long theorized that aging is largely caused by damage to mistakes in gene replication and damage to DNA.
Another study found that the most common type of mutant lamin re-organizes regions of chromosomes that are key in controlling gene expression. These portions of chromosomes, known as heterochromatic regions, are kept inactive for various reasons; for example, one of the two female X chromosomes is inactivated in this fashion in order to avoid having them duplicate the same activities.
One of the hallmarks of the X chromosome heterochromatic region is that it is linked to molecules known as methylated histones. But the researchers found that in a female patient with the syndrome, the levels of methylated histones and of an enzyme required to form them were abnormally low.
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